This application is in response to PAR-09-073 to facilitate the entry of two addiction researchers into the area of functional magnetic resonance imaging (fMRI). We are currently characterizing moment-to-moment changes in cardiovascular arousal in response to emotionally-valenced and appetitive visual cues. This research focus is of substantial public health significance due to the fundamental role of cue reactivity and drug craving in motivating alcohol and drug seeking, use, and relapse following treatment. Visceral changes in autonomic nervous system (ANS) functions contribute significantly to the phenomenal experience of emotional arousal through extensive ANS and central nervous system (CNS) interconnections and the baroreflex. Yet, understanding of dynamic mechanisms that control cue reactivity has been hampered by conceptualizing ANS functions in isolation from the neural system(s) within which they operate. We seek to apply a neurophysiological systems approach to characterize how intra-individual changes in functional, regulatory aspects of emotional arousal in response to environmental cues are integrated across the ANS and CNS. The specific aims are to gain expertise in fMRI methodology and analysis, and to apply this expertise to study a dynamic neural system that modulates cardiovascular response to drug cues. As proof-of-concept, an experiment merging psychophysiological and neuroimaging methodologies is proposed as a fMRI and connectivity analysis learning vehicle (Aim 1) and to examine substantive differences in integrated brain and cardiovascular system response to marijuana-related picture cues in regular marijuana users compared to matched controls who do not use marijuana (Aim 2). fMRI data during cue exposure will be gathered using a 3-Tesla magnet, and the spread of activation between brain regions involved in arousal modulation will be examined using brain connectivity analysis. Activation and connectivity of three brain regions (medial prefrontal cortex, amygdala, brain stem) will be quantitatively linked to cardiovascular modulation within a graph theoretical connectivity model. If successful, this application will yield (1) preliminary support for a new approach wherein ANS reactivity can be linked dynamically (in a time-varying manner, not as a correlation) to neural systems that modulate cue reactivity, (2) new knowledge about how activation in three brain regions interrelates with baroreflex modulation of cardiovascular response to cues, and (3) the groundwork for translational research aimed at evaluating whether biofeedback interventions that improve specific cardiovascular functions can be used to affect inhibition in brain systems that control arousal in response to drug cues. PUBLIC HEALTH RELEVANCE: Cues in the environment, such as the sight of someone smoking, can produce a powerful emotional reaction that increases the likelihood that susceptible individuals will seek or use a drug of choice, even following periods of abstinence. The visceral experience of emotional arousal is an important component of reactivity to drug cues. This application seeks to characterize how the autonomic nervous system works together with the brain to control visceral response to marijuana cues.